Chronic intracellular hypoxia as a clustering and stratifying factor for clinical severity grade in nephrotic syndrome in children

Abstract

Abstract. Nephrotic syndrome is the most common glomerular kidney disease in childhood. It is known that chronic hypoxia is a severe disorder and potent factor of kidney damage. The limited success of existing therapeutic strategies in slowing the progression of chronic kidney disease requires the study of new ways to assess and interpret the levels of chronic intracellular hypoxia concerning basic clinical data, grades of NS activity in children, type of therapeutic response.
 The study aimed to investigate the state of transcription factor and marker of intracellular hypoxia HIF-1alfa in children with different degrees of change in basic clinical and laboratory parameters; to evaluate HIF-1alfa as a possible factor of stratification of activity grade of nephrotic syndrome.
 Methods. This case-control study was carried out in the duration from June 2018 to August 2020. The study was conducted on 35 selected patients with NS collected from the nephrology department, Pediatric Clinical Hospital №7 (Kyiv, Ukraine). Plasma samples were used to measure marker intracellular hypoxia HIF-1alfa. ANOVA followed by the post hoc Kruskal-Wallis test for multiple comparisons was used to test the significance of differences. GraphPad Prism 9.0 Software for Windows and Statistica 10.0 software used. P values <0,05 considered statistically significant.
 Results. Three groups of children with different activity grades were stratified on basis of indicators of proteinuria levels, total blood protein, blood alpha2-globulin levels, serum cholesterol levels, and edema. 1st-grade group found to have a mild increase of HIF-1alfa up to 185-195 a.u. proteinuria 3,5-5,5 g/24 h, total blood protein 47-53 g/L, alfa2-globulins level in blood 20-23 g/L, serum cholesterol level 6-8,5 mMol/L, edema - 1-1.6 points. 2nd grade group found to have moderate increase of HIF-1alfa up to 195,1-205 a.u., proteinuria 5,51-8,5 g/24 h, total blood protein 46,9-40 g/L, alfa2-globulins level in blood 23,1-27 g/L, serum cholesterol level 8.51-10,5 mMol/L, edema 1.61-2.2 points. 3rd-grade group found to have pronounced increase of HIF-1alfa up to 205,1-220 a.u., proteinuria 8,51-14 g/24 h, total blood protein 39,9-32 g/L, alfa2-globulins level in blood 27,1-30 g/L, serum cholesterol level 10.51-13.5 mMol/L, edema 2.21-3 points. Higher HIF-1alfa level appears in children with NS and frequent relapses as compared to the group with rare relapses.
 Conclusion. Thus, the increase of HIF-1 alpha to the level of 185-205 a.u., which corresponds to the I-II degree of activity in children with NS can be used as a starting point and therapeutic window for specific anti-hypoxic and antioxidant interventions. Determination of HIF-1 alpha levels in children with NS can be used as a factor for stratification of the activity grade.